11

Diarrhea

Donald P. Kotler, MD

22

33

44

Intestinal mucosa• Large surface area• Stable ionic microenvironment• Epithelial cell turnover• Epithelial cell maturation• Structural and functional adaptations• Epithelial cell polarity

55

66

77

88

99

Pathophysiology of diarrhea• Osmotic

– decreased surface area– unabsorbable solute

• Secretory– nutrient– toxin– other mediator

• Mixed mechanisms

1010

Pathogenic mechanisms

• Decreased mucosal surface area• Ileal dysfunction• Exudative enteropathy• Inflammatory or tumor-associated

secretagogues• Altered motility

– Slow transit/bacterial overgrowth– Rapid transit

1111

Consequences of intestinal resection

RapidNormalTransit

DecreasedNormalAdaptation

DecreasedNormalB12, bile salt absorption

NormalNormal (if

1212

Partial villus atrophy

Viruses associated with gastroenteritis

• Rotaviruses• Adenoviruses• Caliciviruses• Norwalk like viruses or SRSV (Small Round

Structured Viruses)• Astroviruses• SRV (Small Round Viruses)• Coronaviruses• Toroviruses

1313

Cryptosporidiosis

1414

Celiac disease

Crohn’s ileitis

1515

Diarrhea and ileal resection

1616

1717

Mycobacterium avium

Mycobacterium avium

1818

Cytomegalovirus colitisUlcerative colitis

1919

2020

Serum creatinine concentration

0

1

2

3

4

5

6

9-Oct

10-O

ct

11-O

ct

12-O

ct

13-O

ct

16-O

ct

17-O

ct

19-O

ct

20-O

ct

24-O

ct

26-O

ct

29-O

ct

30-O

ct1-N

ov3-N

ov

190 lb 202 lbWeight

60 liters of IV fluid

220 lb

2121

2222

2323

Practice guidelines for the management of infectious diarrhea

Guidelines - why?

• Response to need for cost effective approach to diagnosis and management

• Evidence-based approach– Identify uncertainties– Grades the quality of the evidence as much as

the evidence itself• Work in progress: needs periodic revision

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Guidelines

• A - Good evidence to recommend

• B - Fair evidence to recommend

• C - Poor evidence to recommend for or against

• D - Fair evidence to recommend against

• E - Good evidence to recommend against

• I - At least 1 RCT• II - At least 1 well-

designed trial– not RCT– cohort, case control,

dramatic uncontrolled studies

• III - Expert opinion

Strength Quality

Diarrhea: magnitude of the problem• Second leading cause of morbidity and mortality

worldwide• >200 million cases of diarrhea per year in the US• 73 million physician consultations, 1.8 million

hospitalizations, 3,100 deaths (mostly in the elderly)• Other morbidities: HUS, Guillain-Barre, malnutrition• Etiology hardly ever determined• Etiologic diagnosis usually is too late to be of clinical

use in outpatients• Often untreated, even if diagnosis is made• The large majority of cases are self-limited in

otherwise healthy children and adults

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The conflict

Cost containment

Widening array of enteric pathogens:enterohemorrhagic E coli, Salmonella, Shigella, Cyclospora, Cryptosporidium, Giardia, Campylobacter jejuni, Clostridium difficile, microsporidia, caliciviruses, other enteric viruses

Etiologic diagnosis: who cares?

• Public health: passive surveillance for common source outbreaks or serious pathogens

• Bioterrorism • Vulnerable populations

– Extremes of life– Malnourished– Immune deficient

2626

Other considerations• Regional and seasonal variation in the US• Globalization• Infections promoted by crowding and

uncertain hygeine– Child care– Schools– Cruise ships

• Decreased recovery with immune deficiency: HIV, immune suppressed, post-transplant, aging

Guidelines• Oral rehydration• Clinical and epidemiological evaluation• Stool tests• Antimicrobial therapy• Antidiarrheals• Available immunizations

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Clinical recommendations• Initial rehydration: ORS A-I

– available commercially– 3.5 gm NaCl, 2.5 gm NaHCO3, 1.5 gm KCl , and 20

gm glucose or glucose polymer per liter of water– glucose can be supplied as sucrose or cooked

cereal flour– Na 90 mM, K 20 mM, Cl 80 mM, HCO3 30 mM,

glucose 111 mM

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Composition of oral solutions

7306903Apple juice

5405003Ginger ale

14511120Sports drink

4500250Chicken soup

31011190WHO-ORSosmolalityGlucoseNa

Na and glucose as mM, osmolality in mosm